Exercise Offers Direct Benefits to the Brain

Now there are even fewer reasons to skip your daily run or that trip to the gym. It’s been well established that regular physical activity can help tone your muscles, prevent cardiovascular disease, and even help alleviate depressive symptoms [see story, "Should Psychiatrists Prescribe Exercise for Depression?"].But exercise also has direct benefit to the brain: Research suggests that it makes physiological changes to neurons resulting in improved cognitive performance.

“Exercise is one lifestyle factor that can modify cognition in the brain both at young and older age,” says Arthur Kramer, a researcher at the University of Illinois at Urbana-Champaign. “There’s been a great deal of work to show it is related to a number of changes in the brain both in terms of structure and function.”

Exercise-induced neurogenesis

Rusty Gage, a researcher at the Salk Institute, studies adult neurogenesis, or the birth of new neurons in the adult brain. There are only a few areas of the brain that show this phenomenon; one in the dentate gyrus, part of the hippocampus, an area implicated in the discrimination and temporal coding of memories [see story, “Physical Fitness Linked to Larger Hippocampus in Elderly”]. More than a decade ago, Gage’s lab discovered that rats that were housed in an enriched environment with toys to play with, tubes to hide in and wheels to run in showed a 15 percent increase in the total volume of the dentate gyrus. To determine which aspects of the environment were responsible for this change, Gage and colleagues separated out the different aspects of the enriched environment. They compared an enriched environment without running wheels to a normal cage with a running wheel.

“Much to our surprise, we saw the biggest increase in the number of neurons that we’d ever seen in animals that had free access to running wheels,” says Gage. “We found that running increases the proliferation of the cells in the dentate gyrus.”

Beyond the increase in volume, the running animals showed significant enhanced learning on simple learning tasks—as well as enhanced long term potentiation, or the cellular mechanism underlying learning and memory, when the group did recordings from single neurons.

Exercise and neurotrophic factor

Time and time again, physical activity has been identified as a key factor for successful aging, defined as improved quality of life and cognition in the elderly. Carl Cotman, a neuroscientist at the University of California, Irvine, wondered if perhaps exercise increased neurotrophic factors, the nourishing proteins that help promote survival in neurons, were somehow involved. [Cotman and Gage are members of the Dana Alliance for Brain Initiatives.]

“When I first looked at the literature, there was nothing there,” says Cotman. “The only papers on exercise and the brain discussed increased glucose metabolism.”

When he and his colleagues started doing experiments, they found that exercise did increase brain-derived neurotrophic factor (BDNF) and learning in an animal model. And subsequent studies demonstrated that exercise also reduced beta-amyloid-beta plaques, a trademark of Alzheimer’s disease, in elderly animals. What’s more, Cotman’s lab has just published research demonstrating that exercise’s beneficial effects last well beyond a single workout.

“In terms of benefiting cognition, the effects are reasonably long-lasting. Even when exercise is stopped, the improvements continue to evolve over the next 7 days in a rodent,” says Cotman. “It’s encouraging. The brain is smart enough to know that exercise helps and tries to continue the programs in the brain that help learning and memory.”

What may be even better news for those who have trouble finding time to get to the gym every single day is that the paper suggests exercising on alternating days is just as beneficial to the brain as exercising every day.

“The data suggest the brain has a lot of tolerance for frequency and amount,” says Cotman.

The mechanism of action

What is it about those 30 minutes of aerobic exercise each day that results in such positive effects? One hypothesis for neurogenesis involves insulin-like growth factor 1 (IGF1), a protein implicated in growth and stress response. There is data to support the idea that exercise increases IGF1 in the blood and passes through the blood-brain barrier to help cell proliferation.

“Exercise also creates enhanced angiogenesis, or blood vessel formation,” says Gage. “When those new vessels are formed, there’s leakiness in the blood brain barrier, so that increased IGF1 in the blood has access to the brain where that proliferation occurs.” Studies when IGF1 is blocked or bound by drugs don’t show the same kind of neurogenesis in exercised animals.

A second hypothesis involves serotonin. Research has shown that running increases the release of serotonin in the brain. When researchers damage serotonin-producing neurons in rodents, neurogenesis is blocked. And if rats are given selective serotonin reuptake inhibitors (SSRIs), a class of drug used to treat depression that inhibit the reuptake of released serotonin by cells, keeping more in circulation, the animals show cell proliferation similar to that of exercised animals.

Cotman argues the regulation of these brain changes is linked to both the neurons themselves and peripheral influences on the brain. But he suggests BDNF is the final common pathway involved in these changes. “It would seem that there are multiple mechanisms that converge into a single mechanism in the brain,” Cotman says. “And I argue that one of the read-outs is BDNF.”

No doubts: Exercise is essential

The researchers continue to work out a deeper understanding of the pathways underlying the exercise/neurogenesis connection. But Cotman, Gage, and Kramer are emphatic about the importance of exercise—there’s no downside and all signs point to its relationship to enhanced learning and successful aging.

“Exercise is free—you don’t need a pill to do it,” says Gage. “I really want to impress on people just how amazing it is and just how broad the impact.”

Cotman wholeheartedly agrees, and his Neuroscience paper is a reminder that you don’t have to be a hard-core triathlete to reap the benefits.

“Exercise is an essential part of health,” he says. “It’s like going to work or doing all those other things in life you have to do, you have to exercise. When you don’t want to, just remind yourself that you need to. And then do it.”